Medullary thymic epithelial cells expressing Aire represent a unique lineage derived from cells expressing claudin.

Abstract:

:The autoimmune regulator Aire is expressed in a small proportion of medullary thymic epithelial cells (mTECs) and is crucial in the induction of central T cell tolerance. The origin and development of Aire(+) mTECs, however, are not well understood. Here we demonstrate that the tight-junction components claudin-3 and claudin-4 (Cld3,4) were 'preferentially' expressed in Aire(+) mTECs. In early ontogeny, Cld3,4(hi) TECs derived from the most apical layer of the stratified thymic anlage first expressed known mTEC markers such as UEA-1 ligand and MTS10. We provide evidence that such Cld3,4(hi) UEA-1(+) TECs represented the initial progenitors specified for Aire(+) mTECs, whose development crucially required NF-kappaB-inducing kinase and the adaptor molecule TRAF6. Our results suggest that Aire(+) mTECs represent terminally differentiated cells in a unique lineage arising during thymic organogenesis.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Hamazaki Y,Fujita H,Kobayashi T,Choi Y,Scott HS,Matsumoto M,Minato N

doi

10.1038/ni1438

subject

Has Abstract

pub_date

2007-03-01 00:00:00

pages

304-11

issue

3

eissn

1529-2908

issn

1529-2916

pii

ni1438

journal_volume

8

pub_type

杂志文章
  • Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self.

    abstract::Naturally arising CD25(+)CD4(+) regulatory T cells actively maintain immunological self-tolerance. Deficiency in or dysfunction of these cells can be a cause of autoimmune disease. A reduction in their number or function can also elicit tumor immunity, whereas their antigen-specific population expansion can establish ...

    journal_title:Nature immunology

    pub_type: 杂志文章,评审

    doi:10.1038/ni1178

    authors: Sakaguchi S

    更新日期:2005-04-01 00:00:00

  • Nr4a receptors are essential for thymic regulatory T cell development and immune homeostasis.

    abstract::Regulatory T cells (T(reg) cells) develop from progenitor thymocytes after the engagement of T cell antigen receptors (TCRs) with high-affinity ligands, but the underlying molecular mechanisms are still unclear. Here we show that the Nr4a nuclear receptors, which are encoded by immediate-early genes upregulated by TCR...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2520

    authors: Sekiya T,Kashiwagi I,Yoshida R,Fukaya T,Morita R,Kimura A,Ichinose H,Metzger D,Chambon P,Yoshimura A

    更新日期:2013-03-01 00:00:00

  • The kinase p38 activated by the metabolic regulator AMPK and scaffold TAB1 drives the senescence of human T cells.

    abstract::In T lymphocytes, the mitogen-activated protein kinase (MAPK) p38 regulates pleiotropic functions and is activated by canonical MAPK signaling or the alternative activation pathway downstream of the T cell antigen receptor (TCR). Here we found that senescent human T cells lacked the canonical and alternative pathways ...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2981

    authors: Lanna A,Henson SM,Escors D,Akbar AN

    更新日期:2014-10-01 00:00:00

  • Serum amyloid A is a soluble pattern recognition receptor that drives type 2 immunity.

    abstract::The molecular basis for the propensity of a small number of environmental proteins to provoke allergic responses is largely unknown. Herein, we report that mite group 13 allergens of the fatty acid-binding protein (FABP) family are sensed by an evolutionarily conserved acute-phase protein, serum amyloid A1 (SAA1), tha...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-020-0698-1

    authors: Smole U,Gour N,Phelan J,Hofer G,Köhler C,Kratzer B,Tauber PA,Xiao X,Yao N,Dvorak J,Caraballo L,Puerta L,Rosskopf S,Chakir J,Malle E,Lane AP,Pickl WF,Lajoie S,Wills-Karp M

    更新日期:2020-07-01 00:00:00

  • Inflammation meets cancer, with NF-κB as the matchmaker.

    abstract::Inflammation is a fundamental protective response that sometimes goes awry and becomes a major cofactor in the pathogenesis of many chronic human diseases, including cancer. Here we review the evolutionary relationship and opposing functions of the transcription factor NF-κB in inflammation and cancer. Although it see...

    journal_title:Nature immunology

    pub_type: 杂志文章,评审

    doi:10.1038/ni.2060

    authors: Ben-Neriah Y,Karin M

    更新日期:2011-07-19 00:00:00

  • TLR-driven early glycolytic reprogramming via the kinases TBK1-IKKɛ supports the anabolic demands of dendritic cell activation.

    abstract::The ligation of Toll-like receptors (TLRs) leads to rapid activation of dendritic cells (DCs). However, the metabolic requirements that support this process remain poorly defined. We found that DC glycolytic flux increased within minutes of exposure to TLR agonists and that this served an essential role in supporting ...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2833

    authors: Everts B,Amiel E,Huang SC,Smith AM,Chang CH,Lam WY,Redmann V,Freitas TC,Blagih J,van der Windt GJ,Artyomov MN,Jones RG,Pearce EL,Pearce EJ

    更新日期:2014-04-01 00:00:00

  • Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide.

    abstract::Despite accumulating evidence that regulatory T cells play a crucial role in preventing autoimmunity, the processes underlying their generation during immune repertoire formation are unknown. We show here that interactions with a single self-peptide can induce thymocytes that bear an autoreactive T cell receptor (TCR)...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/86302

    authors: Jordan MS,Boesteanu A,Reed AJ,Petrone AL,Holenbeck AE,Lerman MA,Naji A,Caton AJ

    更新日期:2001-04-01 00:00:00

  • Author Correction: Alveolar macrophages are epigenetically altered after inflammation, leading to long-term lung immunoparalysis.

    abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title:Nature immunology

    pub_type: 已发布勘误

    doi:10.1038/s41590-020-0739-9

    authors: Roquilly A,Jacqueline C,Davieau M,Mollé A,Sadek A,Fourgeux C,Rooze P,Broquet A,Misme-Aucouturier B,Chaumette T,Vourc'h M,Cinotti R,Marec N,Gauttier V,McWilliam HEG,Altare F,Poschmann J,Villadangos JA,Asehnoune K

    更新日期:2020-08-01 00:00:00

  • Transcription factor T-bet represses expression of the inhibitory receptor PD-1 and sustains virus-specific CD8+ T cell responses during chronic infection.

    abstract::T cell exhaustion has a major role in failure to control chronic infection. High expression of inhibitory receptors, including PD-1, and the inability to sustain functional T cell responses contribute to exhaustion. However, the transcriptional control of these processes remains unclear. Here we demonstrate that the t...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2046

    authors: Kao C,Oestreich KJ,Paley MA,Crawford A,Angelosanto JM,Ali MA,Intlekofer AM,Boss JM,Reiner SL,Weinmann AS,Wherry EJ

    更新日期:2011-05-29 00:00:00

  • Costimulatory blockade by the induction of an endogenous xenospecific antibody response.

    abstract::Xenogeneic tissues induce vigorous T cell immunity, reflecting the ability of costimulatory molecules to function across species barriers. We describe a strategy to inhibit costimulation that exploits species differences using the model of porcine pancreatic islet transplantation into mice. Mice were immunized with ch...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/77853

    authors: Rogers NJ,Mirenda V,Jackson I,Dorling A,Lechler RI

    更新日期:2000-08-01 00:00:00

  • Crystal structure of the human natural killer cell inhibitory receptor KIR2DL1-HLA-Cw4 complex.

    abstract::Inhibitory natural killer (NK) cell receptors down-regulate the cytotoxicity of NK cells upon recognition of specific class I major histocompatibility complex (MHC) molecules on target cells. We report here the crystal structure of the inhibitory human killer cell immunoglobulin-like receptor 2DL1 (KIR2DL1) bound to i...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/87766

    authors: Fan QR,Long EO,Wiley DC

    更新日期:2001-05-01 00:00:00

  • 'Educated' dendritic cells act as messengers from memory to naive T helper cells.

    abstract::Ingested antigens lead to the generation of effector T cells that secrete interleukin 4 (IL-4) rather than interferon-gamma (IFN-gamma) and are capable of influencing naive T cells in their immediate environment to do the same. Using chimeric mice generated by aggregation of two genotypically different embryos, we fou...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1077

    authors: Alpan O,Bachelder E,Isil E,Arnheiter H,Matzinger P

    更新日期:2004-06-01 00:00:00

  • Transcriptomic and epigenetic mechanisms underlying myeloid diversity in the lung.

    abstract::The lung is inhabited by resident alveolar and interstitial macrophages as well as monocytic cells that survey lung tissues. Each cell type plays distinct functional roles under homeostatic and inflammatory conditions, but mechanisms establishing their molecular identities and functional potential remain poorly unders...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-019-0582-z

    authors: Sajti E,Link VM,Ouyang Z,Spann NJ,Westin E,Romanoski CE,Fonseca GJ,Prince LS,Glass CK

    更新日期:2020-02-01 00:00:00

  • Normal T cell homeostasis: the conversion of naive cells into memory-phenotype cells.

    abstract::Weak T cell antigen receptor (TCR) signals from contact with self ligands act in synergy with antiapoptotic signals induced by interleukin 7 (IL-7) to promote the survival of naive T cells in a resting state. The amount of background TCR signaling in naive T cells is set by post-thymic TCR tuning and operates at an in...

    journal_title:Nature immunology

    pub_type: 杂志文章,评审

    doi:10.1038/ni.2018

    authors: Sprent J,Surh CD

    更新日期:2011-06-01 00:00:00

  • TCR sequencing paired with massively parallel 3' RNA-seq reveals clonotypic T cell signatures.

    abstract::High-throughput 3' single-cell RNA-sequencing (scRNA-seq) allows cost-effective, detailed characterization of individual immune cells from tissues. Current techniques, however, are limited in their ability to elucidate essential immune cell features, including variable sequences of T cell antigen receptors (TCRs) that...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-019-0544-5

    authors: Tu AA,Gierahn TM,Monian B,Morgan DM,Mehta NK,Ruiter B,Shreffler WG,Shalek AK,Love JC

    更新日期:2019-12-01 00:00:00

  • Cross-regulation of signaling by ITAM-associated receptors.

    abstract::An important function of receptors that signal through immunoreceptor tyrosine-based activation motifs (ITAMs) is to regulate signaling by heterologous receptors. This review describes mechanisms by which ITAM-associated receptors modulate signaling by Toll-like receptors (TLRs), tumor necrosis factor receptor family ...

    journal_title:Nature immunology

    pub_type: 杂志文章,评审

    doi:10.1038/ni.1706

    authors: Ivashkiv LB

    更新日期:2009-04-01 00:00:00

  • Staging and resetting T cell activation in SMACs.

    abstract::During the productive interaction of T cells with antigen-presenting cells (APCs), engaged receptors, including the T cell antigen receptors and their associated tyrosine kinases, assemble into spatially segregated supramolecular activation clusters (SMACs) at the area of cell contact. Here, we studied intracellular s...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni836

    authors: Freiberg BA,Kupfer H,Maslanik W,Delli J,Kappler J,Zaller DM,Kupfer A

    更新日期:2002-10-01 00:00:00

  • Distinct antibody responses to SARS-CoV-2 in children and adults across the COVID-19 clinical spectrum.

    abstract::Clinical manifestations of COVID-19 caused by the new coronavirus SARS-CoV-2 are associated with age1,2. Adults develop respiratory symptoms, which can progress to acute respiratory distress syndrome (ARDS) in the most severe form, while children are largely spared from respiratory illness but can develop a life-threa...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-020-00826-9

    authors: Weisberg SP,Connors TJ,Zhu Y,Baldwin MR,Lin WH,Wontakal S,Szabo PA,Wells SB,Dogra P,Gray J,Idzikowski E,Stelitano D,Bovier FT,Davis-Porada J,Matsumoto R,Poon MML,Chait M,Mathieu C,Horvat B,Decimo D,Hudson KE,Zot

    更新日期:2021-01-01 00:00:00

  • Regulation of T cell receptor-alpha gene recombination by transcription.

    abstract::Despite the longstanding correlation between transcription and variable-(diversity)-joining (V(D)J) recombination, it is unknown whether transcription itself can direct recombinase targeting. Here we show that blockade of transcriptional elongation through the mouse T cell receptor-alpha (Tcra) locus suppressed V(alph...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1379

    authors: Abarrategui I,Krangel MS

    更新日期:2006-10-01 00:00:00

  • CX3C chemokine mimicry by respiratory syncytial virus G glycoprotein.

    abstract::Chemokines are chemoattractant proteins that are divided into subfamilies based upon cysteine signature motifs termed C, CC, CXC and CX3C. Chemokines have roles in immunity and inflammation that affect cell trafficking and activation of T cells as well as cells of the innate immune system. We report here CX3C chemokin...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/90675

    authors: Tripp RA,Jones LP,Haynes LM,Zheng H,Murphy PM,Anderson LJ

    更新日期:2001-08-01 00:00:00

  • Lineage specification of human dendritic cells is marked by IRF8 expression in hematopoietic stem cells and multipotent progenitors.

    abstract::The origin and specification of human dendritic cells (DCs) have not been investigated at the clonal level. Through the use of clonal assays, combined with statistical computation, to quantify the yield of granulocytes, monocytes, lymphocytes and three subsets of DCs from single human CD34+ progenitor cells, we found ...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.3789

    authors: Lee J,Zhou YJ,Ma W,Zhang W,Aljoufi A,Luh T,Lucero K,Liang D,Thomsen M,Bhagat G,Shen Y,Liu K

    更新日期:2017-08-01 00:00:00

  • The cytotoxic T cell proteome and its shaping by the kinase mTOR.

    abstract::We used high-resolution mass spectrometry to map the cytotoxic T lymphocyte (CTL) proteome and the effect of the metabolic checkpoint kinase mTORC1 on CTLs. The CTL proteome was dominated by metabolic regulators and granzymes, and mTORC1 selectively repressed and promoted expression of a subset of CTL proteins (~10%)....

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.3314

    authors: Hukelmann JL,Anderson KE,Sinclair LV,Grzes KM,Murillo AB,Hawkins PT,Stephens LR,Lamond AI,Cantrell DA

    更新日期:2016-01-01 00:00:00

  • The transcriptional regulator Aire coopts the repressive ATF7ip-MBD1 complex for the induction of immunotolerance.

    abstract::The maintenance of immunological tolerance requires the deletion of self-reactive T cells in the thymus. The expression of genes encoding tissue-specific antigens (TSAs) by thymic epithelial cells is critical for this process and depends on activity of the transcriptional regulator Aire; however, the molecular mechani...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2820

    authors: Waterfield M,Khan IS,Cortez JT,Fan U,Metzger T,Greer A,Fasano K,Martinez-Llordella M,Pollack JL,Erle DJ,Su M,Anderson MS

    更新日期:2014-03-01 00:00:00

  • The transcription factor TCF-1 initiates the differentiation of T(FH) cells during acute viral infection.

    abstract::Induction of the transcriptional repressor Bcl-6 in CD4(+) T cells is critical for the differentiation of follicular helper T cells (T(FH) cells), which are essential for B cell-mediated immunity. In contrast, the transcription factor Blimp1 (encoded by Prdm1) inhibits T(FH) differentiation by antagonizing Bcl-6. Here...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.3229

    authors: Xu L,Cao Y,Xie Z,Huang Q,Bai Q,Yang X,He R,Hao Y,Wang H,Zhao T,Fan Z,Qin A,Ye J,Zhou X,Ye L,Wu Y

    更新日期:2015-09-01 00:00:00

  • Sustained localized expression of ligand for the activating NKG2D receptor impairs natural cytotoxicity in vivo and reduces tumor immunosurveillance.

    abstract::Upregulation of the inducible gene products MICA (human) and Rae-1 (mouse) may promote tumor surveillance and autoimmunity by engaging the activating receptor NKG2D on natural killer (NK) cells and T cells. Nevertheless, sustained expression of MICA by tumors can also elicit NKG2D downregulation, perhaps indicating 'i...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1239

    authors: Oppenheim DE,Roberts SJ,Clarke SL,Filler R,Lewis JM,Tigelaar RE,Girardi M,Hayday AC

    更新日期:2005-09-01 00:00:00

  • The transcription factor BATF operates as an essential differentiation checkpoint in early effector CD8+ T cells.

    abstract::The transcription factor BATF is required for the differentiation of interleukin 17 (IL-17)-producing helper T cells (TH17 cells) and follicular helper T cells (TFH cells). Here we identified a fundamental role for BATF in regulating the differentiation of effector of CD8(+) T cells. BATF-deficient CD8(+) T cells show...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2834

    authors: Kurachi M,Barnitz RA,Yosef N,Odorizzi PM,DiIorio MA,Lemieux ME,Yates K,Godec J,Klatt MG,Regev A,Wherry EJ,Haining WN

    更新日期:2014-04-01 00:00:00

  • Regulating MAVS.

    abstract:: ...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-018-0309-6

    authors: Dempsey LA

    更新日期:2019-02-01 00:00:00

  • Defective survival of naive CD8+ T lymphocytes in the absence of the beta3 regulatory subunit of voltage-gated calcium channels.

    abstract::The survival of T lymphocytes requires sustained, Ca(2+) influx-dependent gene expression. The molecular mechanism that governs sustained Ca(2+) influx in naive T lymphocytes is unknown. Here we report an essential role for the beta3 regulatory subunit of voltage-gated calcium (Ca(v)) channels in the maintenance of na...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.1793

    authors: Jha MK,Badou A,Meissner M,McRory JE,Freichel M,Flockerzi V,Flavell RA

    更新日期:2009-12-01 00:00:00

  • AHR drives the development of gut ILC22 cells and postnatal lymphoid tissues via pathways dependent on and independent of Notch.

    abstract::Innate lymphoid cells (ILCs) of the ILC22 type protect the intestinal mucosa from infection by secreting interleukin 22 (IL-22). ILC22 cells include NKp46(+) and lymphoid tissue-inducer (LTi)-like subsets that express the aryl hydrocarbon receptor (AHR). Here we found that Ahr(-/-) mice had a considerable deficit in I...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2187

    authors: Lee JS,Cella M,McDonald KG,Garlanda C,Kennedy GD,Nukaya M,Mantovani A,Kopan R,Bradfield CA,Newberry RD,Colonna M

    更新日期:2011-11-20 00:00:00

  • A transmembrane CXC chemokine is a ligand for HIV-coreceptor Bonzo.

    abstract::We describe a protein with the hallmarks of a chemokine, designated CXCL16, that is made by dendritic cells (DCs) in lymphoid organ T cell zones and by cells in the splenic red pulp. CXCL16 contains a transmembrane domain and both membrane-bound and soluble forms are produced. Naïve CD8 T cells, natural killer T cells...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/79738

    authors: Matloubian M,David A,Engel S,Ryan JE,Cyster JG

    更新日期:2000-10-01 00:00:00